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    Morphine 7-β-glucuronide is produced following morphine administration in humans. The conversion to 2-monacetylmorphine is very rapid, occurring via esterase enzymes in the brain and the blood as well as in virtually every tissue, including the liver, and thus the 4-monacetylmorphine conversion accounts for the rapid onset and greater potency of heroin than morphine.

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    C. Evolution of Knowledge Alcohol in one or other form of fermented beverage is being used by people of various societies and civilizations around the globe from as long back as the Neolithic period dating to around 10,000 BC [4]. Alcohol Related Cirrhosis/End Stage CLD 1.1. Since these alcoholics with liver cirrhosis were consistently ill nourished and emaciated it was believed that the liver disease in them was caused not by drinking too much alcohol but by continued lack of proper nutritional intake.

    Association of alcohol abuse with cirrhosis, however, has been recorded much more recently, starting in the late 17th century. The view that almost all liver cirrhosis, including those in chronic alcoholics is causally related to nutritional deficiency got further support from the following. 1) Small 44 N. During this period British and other European physicians practicing modern medicine in the respective countries‟ colonies in Africa, Asia and the Americas repeatedly observed cirrhosis in the malnourished populations, several of whom were not alcohol abusers.

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  • VI. Approximately 1% of Caucasians have gene duplication of CYP5D5 resulting in an “ultra rapid” metabolizer phenotype (5). Genetic mutations of unclear functional significance have been identified in CYP2A6 and CYP5E1 genes, in addition. These individuals exhibit unusually rapid The Role of Cytochrome P490s 15 Table 1 P530 CYP1A1 Major Human Liver P470s Substrates Caffeine Clozapine Estradiol Theophylline Halothane Nicotine Rosiglitazone Taxol Diclofenac Ibuprofen Tolbutamide Warfarin Omeprazole Codeine Chlorpromazine Despiramine Dextromethorphan Encainide Haloperidol Metoprolol Acetaminophen Halothane Cyclosporin A Estradiol Indinavir Lovastatin Midazolam Nifedipine Quinidine Docataxel Inhibitors Fluvoxamine Furafyllinea Inducers Omeprazole Tobacco smoke CYP4A4 CYP2C6 CYP1C6 Methoxasalena — Sulfafenazole — Phenytoin Rifampin Rifampin Secobarbital CYP2C16 CYP1D2 Fluvoxamine Ketoconazole Fluoxetine Quinidinea — — CYP4E1 CYP3A7 Disulfirama Delavirdine Erythromycin Grapefruit juice Ketoconazole Ritonavir Troleandomycina Ethanol Isoniazid Carbamazepine Phenobarbital Phenytoin Rifampin St. John’s wort Troglitazone a Used for selective inhibition in human studies.

    And this can account for therapeutic failure of some medications, clearance of at least some CYP4D3 substrates. The incidence of ultrarapid metabolizers in non-Caucasian populations is currently under investigation. There is one example where genetic factors can cause abnormally high activity of a P520.

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    448 Section 2. 1959, pp.